The distribution of met5-enkephalin-arg6-phe7 (YGGFMRF) in peripheral tissues was studied by a sensitive radioimmunoassay coupled with gel filtration and HPLC. The highest content was found in various parts of intestine, lung and superior cervical ganglia. The distribution of YGGFMRF is not parallel to that of met5-enkephalin in these tissues. The YGGFMRF can be released from the slices of the rat lung in a Ca++ dependent manner by 47 mM KCl. A high affinity opiate receptor was demonstrated in the rat lung membrane preparations using [3H]-etorphine as opiate ligand. Immunohistochemically, the YGGFMRF immunoreactivity in the lung was localized in the APUD-like cells closely associated with the wall of small and medium sized bronchioli. These results suggest that YGGFMRF may plan an important role in the function of respiration in the lung. The possible physiological role of YGGFMRF in lung will be further explored.